Structure of human holocarboxylase synthetase gene and mutation spectrum of holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) is an enzyme that catalyzes the incorporation of biotin into apo-carboxylases, and its deficiency causes biotin-responsive multiple carboxylase deficiency. The reported sequences of cDNA for human HLCS from liver, lymphocyte, and KG-1 myeloid cell lines differ at their 5' regions. To elucidate variations of the human HLCS mRNA and longer 5' cDNA ends, we performed screening of the human liver cDNA library and rapid amplification of the cDNA ends (RACE). Our results suggest the existence of three types of HLCS mRNA that start at different exons. The first type starts at exon 1, and the second type starts at exon 3, and both are found in various human tissues. The third type, corresponding to the cDNA from the KG-1 cell, starts at exon 2 of the HLCS gene. Various splicing patterns from exons 3-6 were also observed. None of the variations of cDNA found created a new initiation codon. Mutation screening from exons 6-14, therefore, was sufficient to detect amino acid changes in HLCS in patients. Our direct sequencing strategy for screening mutations in the HLCS gene revealed mutations in five Japanese patients and seven non-Japanese patients. Our analyses involving 12 Japanese and 13 non-Japanese patients and studies by others indicate that (1) there is no panethnically prevalent mutation; (2) the Arg508Trp, Gly581Ser, and Val550Met mutations are found in both Japanese and non-Japanese populations; (3) the IVS10+5G-->A mutation is predominant and probably a founder mutation in European patients; (4) the 655-656insA, Leu237Pro, and 780delG mutations are unique in Japanese patients; (5) the spectrum of the mutations in the HLCS gene may vary substantially among different ethnic groups.

[Central alveolar hypoventilation as a complication of massive intracerebellar hemorrhage: report of a case treated by diaphragm pacing].

The author reported a case of central alveolar hypoventilation (Ondine's curse) which was treated by diaphragm pacing. A 59-year-old man was admitted because of sudden deep coma and tetraparesis. Neurological examination on admission showed miotic pupils with absent light reaction, no oculocephalic reflex, no corneal reflex and tetraparesis. Glasgow scale was evaluated to be E-1 V-1, and M-3 with total of 5 points. Computed tomography confirmed a large hematoma in the cerebellum with ventricular rupture. Immediately, a suboccipital craniectomy was performed and the hematoma was evacuated. His neurological condition was improved gradually within a month after the operation. He responded to verbal orders and moved all his limbs against gravity. His respiration, however, was irregular with a pattern of so-called "cluster breathing" followed by prolonged apnea, that was more pronounced in night. He was suffered from hypoxic hypercapnea and recurrent pneumonia. Therefore, authors decided to employ diaphragm pacing for management of central alveolar hypoventilation. A diaphragm pacemaker (radiofrequency induction) was implanted. A cuff electrode was put around the right phrenic nerve in the right thorax, and the receiver installed subcutaneously in the right anterior chest. Postoperative respiratory study showed ventilation on pacing with satisfactory blood gas and he became able to move around using a wheel chair. In 1966 Glenn demonstrated a new technique to move the diaphragm paced by a receiver through the phrenic nerve, triggered by radio wave from external device.(ABSTRACT TRUNCATED AT 250 WORDS)