Rinsho Shinkeigaku (Clinical Neurology)

Case Report

Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase presenting seizure and psychomotor retardation: a case report

Takeshi Yoshimoto, M.D.1), Takahiro Himeno, M.D.1), Shinichi Takeshima, M.D.1),Shuichiro Neshige, M.D.1), Kenichiro Yamada, Ph.D.2),Yasukazu Yamada, Ph.D.2) and Masaru Kuriyama, M.D., Ph.D.1)

1)Department of Neurology, Brain Attack Center Ota Memorial Hospital
2)Department of Genetics, Institute for Developmental Research, Aichi Human Service Centre

An 18-year-old man was admitted to our hospital because of convulsive seizure. He had psychomotor retardation and intellectual disability from childhood, and had been diagnosed with attention deficit-hyperactivity disorder when he was 12 years old. He showed mental deficit (Wechsler Adult Intelligence Scale-Revised: IQ 52) and tendon hyperreflexia without pathological reflexes, but no involuntary movements or self-injurious behavior. As he had hyperuricemia, we measured the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) in erythrocytes. While HPRT activity had decreased to 57.4% of normal, APRT activity had increased to 140.5% of normal. Genetic analysis revealed a single-base substitution (c.179A>G) in the third exon of the HPRT gene, which resulted in a missense mutation (p.H60R) of the 60th amino acid. His mother was a heterozygous carrier of this mutation and presented partial deficiency (73.3%) of HPRT activity. Lesch Nyhan disease is a neurogenetic disorder caused by complete deficiency of the enzyme HPRT. Variant forms of the disease caused by partial deficiency of HPRT do not show the typical clinical features, or show only mild neurological manifestations; these diseases are jointly referred to as HPRT-related neurological disease (HRND). The present case was unique in that the patient diagnosed as having HRND showed relatively higher HPRT residual activity in erythrocytes.
Full Text of this Article in Japanese PDF (1591K)

(CLINICA NEUROL, 54: 892|896, 2014)
key words: Lesch-Nyhan variant, HPRT, partial deficiency, gene mutation, seizure

(Received: 4-Feb-14)