Richner hanhart syndrome
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《美国医学杂志》
Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
Abstract
Richner Hanhart syndrome is a rare inherited disorder involving the metabolism of tyrosine, a semi-essential amino acid, and it should be considered in the differential diagnosis of a child presenting with ocular and skin lesions. We report a case of Richner Hanhart syndrome in a 19-month-old child, who presented with ocular and skin lesions.
Keywords: Richner Hanhart syndrome; Tyrosinemia
Richner Hanhart syndrome is a rare autosomal recessive disorder of tyrosine metabolism due to the deficiency of the cytosolic fraction of hepatic tyrosine amino transferase.[1] Fewer than 100 cases have been reported,[2] and the majority have been reported from Italy.[3] We report a case of Richner Hanhart syndrome in a 19-month-old female child who presented with eye and skin lesions. This child responded dramatically with dietary restriction of the amino acids phenylalanine and tyrosine.
Case Report
A 19-month-old adopted female child, developmentally normal, was brought with the history of intermittent redness of eyes, lacrimation and photophobia since 6 months of life and thickening of the palms and soles for the past 2 months. On examination she was alert, active with resting heart rate of 82/min, and other vital parameters were normal. She had tender hyperkeratotic papules over the palms and soles. Eye examination showed corneal clouding with dendritic corneal ulcer. She had no gum bleeds, oral ulcers or bony anomalies. She was comfortable on handling and had no bony tenderness. Her higher functions were normal and her developmental quotient assessed using Vineland social maturity scale was 90. Her sensory and motor functions were normal and there were no signs of cerebellar involvement. Examinations of other systems including musculoskeletal system were normal.
Investigations revealed normal blood counts, liver and renal function tests and alpha-feto protein levels. Serum T 3 , free T 4 and TSH levels were within normal limits. Skiagram of chest and both knees and ultrasonogram of the abdomen were also normal. Urine for aminoacid analysis using HPLC revealed increased tyrosine level of 1.09 mg/dl (Control: 0.47±0.21 mg/dl), and blood tyrosine level was 17.97 mg/dl (Control: 5.17±2.55 mg/dl), with normal levels of other aminoacids both in serum and in urine. Serum for succinyl acetone complex was negative and fumaryl acetoacetate hydroxylase level was normal. Hence a diagnosis of Richner Hanhart syndrome was made and the child was started on a diet low in phenylalanine and tyrosine. On follow-up of the child after 4 months, the eye and skin lesions resolved completely and the child is doing well.
Discussion
Richner Hanhart syndrome or tyrosinemia type II (Oculo-cutaneous tyrosinemia) occurs due to the deficiency of enzyme tyrosine amino transferase (TAT). TAT gene is located on chromosome 16q22.1-q 22.3. Richner in 1938 and Hanhart in 1947 described this clinical syndrome independently.[4],[5] Ocular lesions, painful palmo-plantar hyperkeratosis and occasionally mental retardation are the cardinal features of this disease. The eye symptoms develop as early as 2 weeks of age and include redness, lacrimation and photophobia. The eye signs are corneal clouding with central or paracentral corneal opacities, dendritic ulcers and corneal scarring.[6] Deposition of tyrosine crystals in the cornea is responsible for these ocular changes. Skin manifestations usually begin after the first year of life, but may occur as early as the first month of life. The skin manifestations are well demarcated, progressive, painful, nonpruritic hyperkeratotic papules and plaques involving the soles and palms associated with hyperhidrosis. The pain in the soles may be severe enough to prevent ambulation.[7] Mental retardation occurs in less than 50% of patients. Investigations reveal high urinary tyrosine levels with associated high plasma tyrosine levels estimated by tandem mass spectrometric assay. It is rarely necessary to perform a liver biopsy for TAT assay.[8] Dietary restriction of phenylalanine and tyrosine is the key step in the management of these cases.[9] In isolated skin lesions, retinoids can be prescribed either alone or in combination with dietary therapy.[10] In children with severe plantar hyperkeratosis where ambulation is difficult, auto grafts can be placed over these lesions as the disease spares auto grafts.[11] The threshold levels of tyrosine for appearance of clinical manifestation is reported as 1000 umol/L. It is reasonable to keep the blood tyrosine level at 600 umol/L though there is no clear statement in this regard.[8] Richner Hanhart syndrome is a very labile disease, and with good dietary restriction of phenylalanine and tyrosine, there is complete resolution of the eye and skin lesions.[8] The clinical presentation and biochemical defect is different from tyrosinemia type 1 which severely involves the liver, kidneys and the central nervous system and requires treatment with NTBC and liver transplantation. Tyrosinemia type 3 is extremely rare and has predominant neurological involvement.
References
1. Iraj Rezvani. Tyrosine. In Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson, eds. Nelson textbook of Pediatrics . 17th edn. Philadelphia; W.B. Saunders, 2004; 402-405.
2. Tallab TM. Richner Hanhart syndrome: importance of early diagnosis and intervention. J Am Acad Dermatol 1996; 35 : 857-859.
3. Fois A, Borgogni P, Cioni M et al. Presentation of the data of the Italian registry for oculocutaneous tyrosinemia. J Inherited metab dis. 1986; 9 (suppl): S 262-263.
4. Richner H. Hornhautaffektion bei keratoma palmare et plantare hereditarium. Klin Mbl Augenheilk 1938; 100 : 580-588.
5. Hanhart E. Neue Sonderformen von keratosis palmo-plantaris, u.a.eine regelmaessig-dominante mit systematisierten Lipomen, ferner 2 einfach-rezessive mit Schwachsinn und z.T.mit Hornhautveraenderungen des Auges (Ektodermatosyndrom). Dermatologica 1947; 94: 286-308.
6. Goldsmith LA. Tyrosinemia II: Lessons in molecular pathophysiolosy. Pediatr dermatol 1983; 1 : 25-34.
7. Rabinowitz LG, Williams LR, Anderson CE et al. Painful koratoderma and photophobia: hallmarks of tyrosinemia type II . J Pediatr 1995; 126: 266-269.
8. M. Al -Essa, M. Rashed, P. T. ozand . Tyrosinemia type II: Report of the first four cases in Saudi Arabia - available from URL : http : //www. Kfshrc.edu.sa/annals/ 185/97-329. html. Accessed May 20.
9. Machino H, Miki Y, Kawatsu T et al. Successful dietary control of tyrosinemia II. J Am Aced Dermatol 1983; 9: 533-9.
10. Podglajen-wecx steno, Delaporte E, Piette F et al. Oculocutaneous type 2 tyrosinemia. Ann Dermatol Venereol 1993; 170 : 139-142.
11. Crovato F, Desirello G, Gatti R, Babbini N, Reboras A. Richner- Hanhart syndrome spares a plantar auto graft. Arch Derm 1985; 121 : 539-540.(Janakiraman Lalitha, Sath)
Abstract
Richner Hanhart syndrome is a rare inherited disorder involving the metabolism of tyrosine, a semi-essential amino acid, and it should be considered in the differential diagnosis of a child presenting with ocular and skin lesions. We report a case of Richner Hanhart syndrome in a 19-month-old child, who presented with ocular and skin lesions.
Keywords: Richner Hanhart syndrome; Tyrosinemia
Richner Hanhart syndrome is a rare autosomal recessive disorder of tyrosine metabolism due to the deficiency of the cytosolic fraction of hepatic tyrosine amino transferase.[1] Fewer than 100 cases have been reported,[2] and the majority have been reported from Italy.[3] We report a case of Richner Hanhart syndrome in a 19-month-old female child who presented with eye and skin lesions. This child responded dramatically with dietary restriction of the amino acids phenylalanine and tyrosine.
Case Report
A 19-month-old adopted female child, developmentally normal, was brought with the history of intermittent redness of eyes, lacrimation and photophobia since 6 months of life and thickening of the palms and soles for the past 2 months. On examination she was alert, active with resting heart rate of 82/min, and other vital parameters were normal. She had tender hyperkeratotic papules over the palms and soles. Eye examination showed corneal clouding with dendritic corneal ulcer. She had no gum bleeds, oral ulcers or bony anomalies. She was comfortable on handling and had no bony tenderness. Her higher functions were normal and her developmental quotient assessed using Vineland social maturity scale was 90. Her sensory and motor functions were normal and there were no signs of cerebellar involvement. Examinations of other systems including musculoskeletal system were normal.
Investigations revealed normal blood counts, liver and renal function tests and alpha-feto protein levels. Serum T 3 , free T 4 and TSH levels were within normal limits. Skiagram of chest and both knees and ultrasonogram of the abdomen were also normal. Urine for aminoacid analysis using HPLC revealed increased tyrosine level of 1.09 mg/dl (Control: 0.47±0.21 mg/dl), and blood tyrosine level was 17.97 mg/dl (Control: 5.17±2.55 mg/dl), with normal levels of other aminoacids both in serum and in urine. Serum for succinyl acetone complex was negative and fumaryl acetoacetate hydroxylase level was normal. Hence a diagnosis of Richner Hanhart syndrome was made and the child was started on a diet low in phenylalanine and tyrosine. On follow-up of the child after 4 months, the eye and skin lesions resolved completely and the child is doing well.
Discussion
Richner Hanhart syndrome or tyrosinemia type II (Oculo-cutaneous tyrosinemia) occurs due to the deficiency of enzyme tyrosine amino transferase (TAT). TAT gene is located on chromosome 16q22.1-q 22.3. Richner in 1938 and Hanhart in 1947 described this clinical syndrome independently.[4],[5] Ocular lesions, painful palmo-plantar hyperkeratosis and occasionally mental retardation are the cardinal features of this disease. The eye symptoms develop as early as 2 weeks of age and include redness, lacrimation and photophobia. The eye signs are corneal clouding with central or paracentral corneal opacities, dendritic ulcers and corneal scarring.[6] Deposition of tyrosine crystals in the cornea is responsible for these ocular changes. Skin manifestations usually begin after the first year of life, but may occur as early as the first month of life. The skin manifestations are well demarcated, progressive, painful, nonpruritic hyperkeratotic papules and plaques involving the soles and palms associated with hyperhidrosis. The pain in the soles may be severe enough to prevent ambulation.[7] Mental retardation occurs in less than 50% of patients. Investigations reveal high urinary tyrosine levels with associated high plasma tyrosine levels estimated by tandem mass spectrometric assay. It is rarely necessary to perform a liver biopsy for TAT assay.[8] Dietary restriction of phenylalanine and tyrosine is the key step in the management of these cases.[9] In isolated skin lesions, retinoids can be prescribed either alone or in combination with dietary therapy.[10] In children with severe plantar hyperkeratosis where ambulation is difficult, auto grafts can be placed over these lesions as the disease spares auto grafts.[11] The threshold levels of tyrosine for appearance of clinical manifestation is reported as 1000 umol/L. It is reasonable to keep the blood tyrosine level at 600 umol/L though there is no clear statement in this regard.[8] Richner Hanhart syndrome is a very labile disease, and with good dietary restriction of phenylalanine and tyrosine, there is complete resolution of the eye and skin lesions.[8] The clinical presentation and biochemical defect is different from tyrosinemia type 1 which severely involves the liver, kidneys and the central nervous system and requires treatment with NTBC and liver transplantation. Tyrosinemia type 3 is extremely rare and has predominant neurological involvement.
References
1. Iraj Rezvani. Tyrosine. In Richard E. Behrman, Robert M. Kliegman, Hal B. Jenson, eds. Nelson textbook of Pediatrics . 17th edn. Philadelphia; W.B. Saunders, 2004; 402-405.
2. Tallab TM. Richner Hanhart syndrome: importance of early diagnosis and intervention. J Am Acad Dermatol 1996; 35 : 857-859.
3. Fois A, Borgogni P, Cioni M et al. Presentation of the data of the Italian registry for oculocutaneous tyrosinemia. J Inherited metab dis. 1986; 9 (suppl): S 262-263.
4. Richner H. Hornhautaffektion bei keratoma palmare et plantare hereditarium. Klin Mbl Augenheilk 1938; 100 : 580-588.
5. Hanhart E. Neue Sonderformen von keratosis palmo-plantaris, u.a.eine regelmaessig-dominante mit systematisierten Lipomen, ferner 2 einfach-rezessive mit Schwachsinn und z.T.mit Hornhautveraenderungen des Auges (Ektodermatosyndrom). Dermatologica 1947; 94: 286-308.
6. Goldsmith LA. Tyrosinemia II: Lessons in molecular pathophysiolosy. Pediatr dermatol 1983; 1 : 25-34.
7. Rabinowitz LG, Williams LR, Anderson CE et al. Painful koratoderma and photophobia: hallmarks of tyrosinemia type II . J Pediatr 1995; 126: 266-269.
8. M. Al -Essa, M. Rashed, P. T. ozand . Tyrosinemia type II: Report of the first four cases in Saudi Arabia - available from URL : http : //www. Kfshrc.edu.sa/annals/ 185/97-329. html. Accessed May 20.
9. Machino H, Miki Y, Kawatsu T et al. Successful dietary control of tyrosinemia II. J Am Aced Dermatol 1983; 9: 533-9.
10. Podglajen-wecx steno, Delaporte E, Piette F et al. Oculocutaneous type 2 tyrosinemia. Ann Dermatol Venereol 1993; 170 : 139-142.
11. Crovato F, Desirello G, Gatti R, Babbini N, Reboras A. Richner- Hanhart syndrome spares a plantar auto graft. Arch Derm 1985; 121 : 539-540.(Janakiraman Lalitha, Sath)