Diagnostic Criteria

No consensus clinical diagnostic criteria for TCIRG1-related osteopetrosis have been published.

Suggestive Findings

TCIRG1-related osteopetrosis should be suspected in probands with the following clinical, laboratory, and imaging findings and family history.

Clinical findings

Source: GeneReviews — "TCIRG1-Related Osteopetrosis"

Differential Diagnosis

Other disorders with phenotypes overlapping that of TCIRG1-related osteopetrosis are listed in . Note: Pathogenic variants in TCIRG1 account for 58% of autosomal recessive osteopetrosis. Other genes associated with autosomal recessive osteopetrosis include CLCN7 (13% of autosomal recessive osteopetrosis) , OSTM1 (5%) , and SNX10 (4%) . Table 3. Genes of Interest in the Differential Diagnosis of TCIRG1-Related Osteopetrosis

Management Guidelines

No clinical practice guidelines for TCIRG1-related osteopetrosis have been published, although general guidelines for the management of osteopetrosis have been compiled . In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder and recommendations from published literature.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual with TCIRG1-related osteopetrosis, the evaluations summarized in are recommended (if not performed as part of the evaluation that led to the diagnosis).

Table 4.

TCIRG1-Related Osteopetrosis: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Skeletal

| • Skeletal survey incl assessment for osteopetrorickets (bilateral wrist knee radiographs) in infants children

• Consult orthopedic surgeon for any fractures skeletal deformities detected.

| Material properties of osteopetrotic bone introduce many challenges to operative repairs incl resistance to drilling high risk of iatrogenic fractures.

Respiratory

| Assess for respiratory compromise frequent infections in those w/small-volume thorax. |

Mineral homeostasis

| Serum calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, intact parathyroid hormone |

Blood dyscrasia/ Bone marrow failure

| • CBC w/differential

• Reticulocyte count

• Platelet count

| • Anemia thrombocytopenia reflect bone marrow sclerosis.

• Leukopenia is variable.

Hemolysis

...

Source: GeneReviews — "TCIRG1-Related Osteopetrosis"

Clinical Guidance

High-dose calcitriol. Though not performed on mice with TCIRG1-related osteopetrosis studies, studies in mice with CLCN7-related autosomal dominant osteopetrosis have shown that high-dose calcitriol might be detrimental and actually increase bone mass . Note: Low-dose calcitriol is given to prevent seizures and protect against bone pain and skeletal deformities in those with hypocalcemia and/or hypophosphatemia.

Source: GeneReviews — "TCIRG1-Related Osteopetrosis"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "TCIRG1-Related Osteopetrosis"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. The frequency of surveillance is for general guidance only and may need to be adjusted depending on the rapidity with which complications of TCIRG1-related osteopetrosis evolve in a given individual. Table 7. TCIRG1-Related Osteopetrosis: Recommended Surveillance

Source: GeneReviews — "TCIRG1-Related Osteopetrosis"