Case Report
Clinical Genetics 1990: 38: 155-1 59
Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion E. LEGIUS',E. BATEN', M. STUL',P. MARYNEN' AND J.-J. CAWMAN' 'Center for Human Genetics, University Hospital Gasthuisberg, Leuven, and 'A. Z. St Lucas, St Jozef General Hospital, Brugge, Belgium Somatic mosaicism for a deletion in the ornithine transcarbamylase gene is described in a boy with sporadic late onset ornithine transcarbamylase deficiency. These findings are discussed in relation to the clinical picture of the patient and in relation to genetic counseling. Received 27 October 1989, revised 23 February, accepted f o r publication 24 February 1390
Key words: deletion; DNA; genetic counsehg; inborn error of metabolism; mosaicism; OTC gene
Ornithine transcarbamylase (OTC) deficiency, the most common heritable urea cycle defect, is an X-linked disorder and is associated in boys with severe hyperammonemia, coma, convulsions and death in the neonatal period. However. some boys with OTC deficiency have only a partial enzyme deficiency with onset of symptoms after the neonatal period. They have a remarkably better prognosis and even have a chance of surviving without brain damage (Drogari & Leonard 1988, Brusilow & Horwich 1989). Most female camers are asymptomatic, but some 20% develop symptoms with hyperammonemia and eventually brain damage (Batshaw et al. 1986). Asymptomatic female carriers can mostly be diagnosed after a protein load (Hokanson et al. 1978), allopurinol testing (Brusilow & Valle 1987), or by analysis of restriction fragment length polymorphisms
(RFLP) in or around the gene in familial cases (Rozen et al. 1986). Recently we had the opportunity to study alterations in the OTC gene of a boy with mild OTC deficiency diagnosed at the age of 8 months. Material and Methods
Pa tien t S.G., a boy, was the first child born to healthy and unrelated parents. The first symptoms, vomiting and failure to thrive, were noted at the age of 6 months after the introduction of meat into the diet. Two months later, mild OTC deficiency was suspected because of the following biochemical abnormalities: plasma ammonia 323 pg/dl (NL
Clinical Genetics 1990: 38: 155-1 59
Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion E. LEGIUS',E. BATEN', M. STUL',P. MARYNEN' AND J.-J. CAWMAN' 'Center for Human Genetics, University Hospital Gasthuisberg, Leuven, and 'A. Z. St Lucas, St Jozef General Hospital, Brugge, Belgium Somatic mosaicism for a deletion in the ornithine transcarbamylase gene is described in a boy with sporadic late onset ornithine transcarbamylase deficiency. These findings are discussed in relation to the clinical picture of the patient and in relation to genetic counseling. Received 27 October 1989, revised 23 February, accepted f o r publication 24 February 1390
Key words: deletion; DNA; genetic counsehg; inborn error of metabolism; mosaicism; OTC gene
Ornithine transcarbamylase (OTC) deficiency, the most common heritable urea cycle defect, is an X-linked disorder and is associated in boys with severe hyperammonemia, coma, convulsions and death in the neonatal period. However. some boys with OTC deficiency have only a partial enzyme deficiency with onset of symptoms after the neonatal period. They have a remarkably better prognosis and even have a chance of surviving without brain damage (Drogari & Leonard 1988, Brusilow & Horwich 1989). Most female camers are asymptomatic, but some 20% develop symptoms with hyperammonemia and eventually brain damage (Batshaw et al. 1986). Asymptomatic female carriers can mostly be diagnosed after a protein load (Hokanson et al. 1978), allopurinol testing (Brusilow & Valle 1987), or by analysis of restriction fragment length polymorphisms
(RFLP) in or around the gene in familial cases (Rozen et al. 1986). Recently we had the opportunity to study alterations in the OTC gene of a boy with mild OTC deficiency diagnosed at the age of 8 months. Material and Methods
Pa tien t S.G., a boy, was the first child born to healthy and unrelated parents. The first symptoms, vomiting and failure to thrive, were noted at the age of 6 months after the introduction of meat into the diet. Two months later, mild OTC deficiency was suspected because of the following biochemical abnormalities: plasma ammonia 323 pg/dl (NL
